Dept of Radiology, School of Medicine and Dentistry, The University of Rochester. Rochester, N.Y.

Presented before the Radiological Society of North America at the 28th Annual Meeting in Chicago ILL. Nov 30 - Dec 4 1942 and submitted for publication June 1944. __________________________________________________________________

Prior to its clinical use, ethyl iodophenyundecylate was tested intrathecally in dogs in a series of comparative experiments against iodized poppy-seed oil. In these tests the new medium proved to be much easier to handle, produced discomfort of shorter duration, and in most of the animals was almost completely absorbed within a year. The clinical results have paralleled those obtained in animal experimentation.

These studies were aided by a grant from the Research Laboratories of the Eastman Kodak Company.

Because the new medium is so fluid, it is easily injected or removed with an 18 - or 20- gauge needle. Following intrathecal injection of 3 to 5 cc of ethyl iodophenylundecylate in dogs, there is a period of slight fever, lasting one or two days.

The size of cysts with ethyl iodophenylundecylate is considerably less than that of those produced by iodized poppy-seed oil; this is probably referable to the greater viscosity of the poppy-seed oil. Cord sections taken at intervals from dogs injected intrathecally with ethyl iodophenylundecylate show that the physiological response about the cysts is essentially a foreign body reaction.

Acute toxicities for ethyl iodophenylundecylate were determined by intraperitoneal and intravenous injections. The LD 50 for intraperitoneal injections was found to be 4.6 gm./kilogram for mice and 19 gm./kilogram for rats. Intravenous injections in dogs showed that ethyl iodophenylundecylate was without effect at a level of 0.5 gm./kilogram but was lethal at a level of 1.0 gm./kilogram. With the assurance from these experimental studies that the new medium was safe it was first tested clinically on Nov 23, 1940, by Drs Paul Garvey and Nathaniel Jones in Case I reported below [in article] the absence of untoward developments led to its use in 4 additional patients.

The most extensive series of cases (3) (As of November 1942) have been compiled by Dr William P Van Wagenen (Rochester, N.Y.) Dr R. Glen Spurling (Louisville, Ky) and Dr William V. Cone (Montreal, Canada). From their experience it is evident that the best results are obtained if 3 to 5 c.c. of ethyl iodophenylundecylate are injected and later removed by the general procedure of Kubik and Hampton (3). In this way up to 90% of the injected medium is easily removed and the small amount of residuum is completely absorbed within a few weeks.

CASE HISTORIES.

Case 1. (in short) 53 male, complete paralysis from waist down 5cc of ethyl iodophenylundecylate was injected after 8 cc of crystal clear CSF. Patient died 17 days later from a rupture of [a] aneurysm. A postmortem examination showed that the contrast medium was still mobile. Spinal cord showed a few polymorphonuclear cells around the nerve roots. There was no evidence of encystment in any portion of the cord.

Case 2. (in short) 28 male (white) with embryoma of the left testicle with bone and pulmonary metastases was injected with 5 cc of ethyl iodophenylundecylate on Jan 7 1941. Films (Fig 2) taken at intervals up to May 29th 1941 show a gradual absorption of over half of the injected contrast medium. Immediately after injection the Pantopaque became immobile as a result of filling the nerve sheaths, particularly the sheaths of the sciatic nerves. During the week immediately following the injection, the patient had a slight paresthesia in the lower leg. Otherwise there were no clinical symptoms. Death occurred at home and an autopsy was not obtained.

Case 3. (in short) 29 year old female with clinical symptoms of a ruptured nucleus pulposus was injected on Sept 9 1942, with 3 c.c. of ethyl iodophenylundecylate. A diagnosis of extra-medullary compression between L4 and L5 was somewhat equivocal. The contrast was removed. On the Sept 21 1942 3 c.c of Pantopaque was again injected, but fluoroscopy showed that some of it was extradural.

For several days the patient experienced increased leg pain, especially after manipulation. Finally, on Sept 28, 1942 a third examination was made with 3 c.c. of ethyl iodophenylundecylate and a positive diagnosis of a lesion at the disk space of L4 on the left side was obtained. A laminectomy was performed on Sept 30. A section taken at the probable site of the extradural injection showed striated muscle and fibrous tissue.

In the section reproduced in Figure 4 (MF: Not available) dense fibrous connective tissue is seen having a structure consistent with that of ligamentum flvum. In this tissue there is no evidence of any inflammatory reaction. Other portions of the section show striated muscle and areas of fairly loose connective tissue. Some of the striated muscle bundles appear to contain more than their normal number of nuclei, while others show considerable degenerative change.

Instead of normal striated myofibrils the muscle sheaths contain a granular debris. This degeneration could be due to some local irritant, but similar changes are often seen without any foreign matter in the vincity. Several areas of the less dense connective tissue show infiltration by polymorphonuclear leukocytes in addition to many small round cells and a few larger monocysts. No definite droplets of contrast medium are seen, and there is no localized focal necrosis or abscess formation.

DISCUSSION.(Please note the Speakers name, Capt Frank H. Mayfiels, M.C.) Pantopaque has solved many problems. It is a much less viscid oil than Lipiodol, it moves within the spinal canal more rapidly, and because of its lessened surface tension it fills the root sleeves better and does not show false filling defects. Furthermore, it is easily removed. In most instances, one can recover by simple aspiration nearly all of the material, the usual experience being to leave one ot two minute droplets. The highest cellular reaction was one thousand cells at the end of 48 hours. The usual count after administration of Pantopaque was 25 to 50 cells. This is almost identical with our experience with Lipiodol. In think, therfore, that the toxic potentialities of the two drugs are the same.

Pantopaque, however, has two outstanding advantages. First, it is a more satisfactory medium for diagnostic purposes. Second, it can be removed more completely and more easily than Lipiodol, thereby overcoming the ONE OUTSTANDING OBJECTION to the use of contrast medium, namely, the MEDICO-LEGAL objection to leaving in the spinal canal a foreign body which is VISIBLE on the x-ray plate. Dr Strain has mentioned the comparative absorbability of Pantopaque and Lipiodol, and from my experience I find Pantopaque is absorbed, OR RATHER LOSES ITS RADIOPACITY. END

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